A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Upadacitinib in Subjects With Active Ankylosing Spondylitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 187
- 试验地点
- 101
- 主要终点
- Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 14
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of upadacitinib in participants with active ankylosing spondylitis (AS) who have had an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (NSAIDs) or intolerance to or a contraindication for NSAIDs, and who are naïve to biologic disease-modifying anti-rheumatic drugs (bDMARD).
详细描述
This study includes two periods: a 14-week double-blind placebo-controlled period and a 90-week open-label long-term extension period.
Eligible participants were randomly assigned in a 1:1 ratio to receive upadacitinib 15 mg or placebo for 14 weeks in Period 1.
Participants who completed Period 1 received upadacitinib 15 mg for 90 weeks in the extension period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant with a clinical diagnosis of ankylosing spondylitis (AS) and meeting the modified New York criteria for AS.
- •Participant must have baseline disease activity as defined by having a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >= 4 and a Patient's Assessment of Total Back Pain score >= 4 based on a 0 - 10 numeric rating scale (NRS) at the Screening and Baseline visits.
- •Participant has had an inadequate response to at least two nonsteroidal anti-inflammatory drugs (NSAIDs) over an at least 4-week period in total at maximum recommended or tolerated doses, or participant has an intolerance to or contraindication for NSAIDs as defined by the Investigator.
- •If entering the study on concomitant methotrexate (MTX), leflunomide, sulfasalazine (SSZ), and/or hydroxychloroquine, participant must be on a stable dose of MTX (<= 25 mg/week) and/or SSZ (<= 3 g/day) and/or hydroxychloroquine (<= 400 mg/day) or leflunomide (<= 20 mg/day) for at least 28 days prior to the Baseline visit. A combination of up to two background conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is allowed except the combination of MTX and leflunomide.
- •If entering the study on concomitant oral corticosteroids, participant must be on a stable dose of prednisone (<= 10 mg/day), or oral corticosteroid equivalents, for at least 14 days prior to the Baseline visit.
- •If entering the study on concomitant NSAIDs, tramadol, combination of acetaminophen and codeine or hydrocodone, and/or non-opioid analgesics, participant must be on stable dose(s) for at least 14 days prior to the Baseline visit.
排除标准
- •Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- •Prior exposure to any biologic therapy with a potential therapeutic impact on spondyloarthritis (SpA).
- •Intra-articular joint injections, spinal/paraspinal injection(s), or parenteral administration of corticosteroids within 28 days prior to the Baseline visit. Inhaled or topical corticosteroids are allowed.
- •Participant on any other DMARDs (other than those allowed), thalidomide or apremilast within 28 days or five half-lives (whichever is longer) of the drug prior to the Baseline visit.
- •Participant on opioid analgesics (except for combination acetaminophen/codeine or acetaminophen/hydrocodone which are allowed) or use of inhaled marijuana within 14 days prior to the Baseline visit.
- •Participant has a history of inflammatory arthritis of different etiology other than axial SpA (including but not limited to rheumatoid arthritis, psoriatic arthritis, mixed connective tissue disease, systemic lupus erythematosus, reactive arthritis, scleroderma, polymyositis, dermatomyositis, fibromyalgia), or any arthritis with onset prior to 17 years of age.
- •Laboratory values meeting the following criteria within the Screening period prior to the first dose of study drug: serum aspartate transaminase > 2 × upper limit of normal (ULN); serum alanine transaminase > 2 × ULN; estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease formula < 40 milliliter (mL)/minute/1.73m^2; hemoglobin < 10 gram/deciliter, total white blood cell count < 2,500/microliter (μL); absolute neutrophil count < 1,500/μL; absolute lymphocyte count < 800/μL; and platelet count < 100,000/μL.
研究组 & 干预措施
Upadacitinib 15 mg
Participants will receive 15 mg upadacitinib orally once a day for 14 weeks in Period 1 and continue to receive 15 mg upadacitinib orally once a day for an additional 90 weeks in Period 2.
干预措施: Upadacitinib (Drug)
Placebo
Participants will receive matching placebo orally once a day for 14 weeks in Period 1. In Period 2 participants will receive 15 mg upadacitinib orally once a day for 90 weeks.
干预措施: Upadacitinib (Drug)
Placebo
Participants will receive matching placebo orally once a day for 14 weeks in Period 1. In Period 2 participants will receive 15 mg upadacitinib orally once a day for 90 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 14
时间窗: Baseline and Week 14
ASAS 40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of \> 0 units) in the potential remaining domain: * Patient's global assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (no activity) to 10 (severe activity); * Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe pain); * Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible); * Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 \[level of stiffness\] and 6 \[duration of stiffness\]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
次要结局
- Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 14(Baseline and Week 14)
- Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) Partial Remission(Week 14)
- Change From Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment at Week 14(Baseline and Week 14)
- Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Score(Baseline and Week 14)
- Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMI[Lin]) at Week 14(Baseline and Week 14)
- Change From Baseline in SPARCC MRI Score for Sacroiliac Joints at Week 14(Baseline and Week 14)
- Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 14(Baseline and Week 14)
- Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for the Spine at Week 14(Baseline and Week 14)
- Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 14(Baseline and Week 14)
- Percentage of Participants With Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Week 14(Baseline and Week 14)
- Percentage of Participants Achieving an ASAS 20 Response at Week 14(Baseline and Week 14)
- Change From Baseline in ASAS Health Index (HI) at Week 14(Baseline and Week 14)